Immunotherapy - the greatest cancer hack ever

Your body’s own immune system is the best weapon against cancer. That’s the claim behind one of the latest developments in cancer treatment, called immuno-oncology, a specialised type of immunotherapy. Our team of medical writers recently created a digital learning resource for a ground-breaking clinical trial investigating the safety and efficacy of a cancer immunotherapy to treat an aggressive variant of lymphoma. This immunotherapy technique involved extracting immune T-cells, a type of white blood cell, ‘weaponising’ them in a laboratory and then reintroducing them into the patient in the hope of inducing an anti-cancer effect. This is a fascinating area of cancer research that is rapidly gaining attention in the world of cancer immunotherapy.

 

Why is immunotherapy and immuno-oncology a big deal?

The immune system is able to to recognise and eliminate cancers, making it an ideal anti-cancer agent. Cancer immunotherapy was one of the most heavily invested areas of 2017, highlighting the pharmaceutical industry’s eagerness to harness this potential. Most experts recognise the potential of immuno-oncology and there’s great excitement about this new age in cancer therapy. More than just a new treatment type, it gives us a new way to look at cancer – and a reason to better understand the body’s natural defences.

Traditionally, cancer has been treated using chemotherapy, radiotherapy, surgery, and other targeted therapies. However, a greater understanding of molecular oncology and the complex interaction between cancer cells and our immune systems, immunotherapies may become the ‘fifth pillar’ of cancer treatment. There are already effective immunotherapies for treating cancer types such as melanoma and lymphoma, as well as lung, kidney and bladder carcinoma.

 

Cancer immunotherapy has the potential to produce excellent clinical outcomes. However, immuno-oncology is a rapidly developing field of medicine where significant gaps in our understanding remain.

 

How does immuno-oncology work?

Normally, the immune system recognises and eliminates tumours through a process known as immunosurveillance. However, many cancer types avoid detection and so develop further; this is because the tumour is able to remain ‘invisible’ and unresponsive to normal immune regulation. The tumour is also able to suppress immune responses within its immediate vicinity. Anti-cancer immunotherapies aim to re-establish the body’s anti-tumour capability without causing various autoimmune-related issues.

 

Established cancer immunotherapy treatments

A wide range of cancer immunotherapy approaches have proven effective; lets take a look at some of these therapies below.

 

Monoclonal antibodies (mABs)

mABs have been a major treatment for a diverse range of cancers for the past 20 years. These proteins bind to specific antigens on the surface of the cancer cell. These proteins block cancer signalling pathways, recruit components of the immune system, or allow delivery of chemotherapy drugs, radioactive particles, or cancer-killing toxins into the cancer cells.

Immunomodulatory mABs, or checkpoint inhibitors, instead of directly interacting with the cancer cell target the immunosuppression that tumours induce. These molecules stop tumour cells from suppressing T-cell activity, and so produce a prolonged anti-cancer response. Approved checkpoint inhibitors currently block programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4), both found on T-cells, as well as programmed death ligand 1 (PD-L1), which is found on tumour cells.

 

Cytokines

These signalling molecules play a critical role in mounting an effective immune response against tumour cells. Interferons (Intron® A (Interferon α-2b) and interleukins (Proleukin®/aldesleukin (IL-2)) are two types of cytokine used to treat cancer. They prevent cancer cell growth by stimulating and recruiting immune cells and encouraging cancer cells to release signals that make them more ‘visible’ to the body’s circulating immune cells.

 

The future of cancer immunotherapy

 

Adoptive cell transfer (ACT)

Chimeric antigen receptor T-cell therapy (CAR-T) involves collecting T-cells, genetically engineering them and then growing them in large numbers in a laboratory. These immune cells are redesigned to react against a specific tumour antigen and reintroduced into the patient to eradicate the cancerous cells.

 

A study recently published in the journal Nature Medicine has reported that a female patient with advanced metastatic breast cancer has been completely cleared of cancer using adoptive cell transfer.

 

Genetic analysis of her tumour biopsies identified four genetic abnormalities that were responsible for several mutated proteins. Researchers harvested a specific type of immune cell, known as tumour infiltrating lymphocytes (TILs), from these biopsies and screened them to identify the variants that would be most effective at invading and recognising these mutated proteins. They then grew the selected TILs in large quantities before introducing approximately 80 billion of them, alongside IL-2 and pembrolizumab, into her body. The woman was reported as cancer free at 42 weeks following treatment and has remained so to this day. Remarkably, the researchers detected the reintroduced TILs in the woman’s body approximately 17 months post treatment, indicating a potent and durable anti-cancer effect. This is an extraordinary success, since breast cancers are known for having very few mutations, which makes them more difficult for the immune system to detect.

 

Recently two CAR-T therapies, Yescarta® (axicabtagene ciloleucel) and KYMRIAH® (tisagenlecleucel), were approved for use on the NHS in England. Both are indicated for blood cancers and offer a crucial new option for the few patients where traditional chemotherapy has failed.

 

Cancer immunotherapy vaccines

Therapeutic cancer vaccines act by stimulating the immune system into producing antibodies that bind to specific antigens found on a tumour cell. The immune system then initiates a potent anti-tumour response, eradicating the malignant cells. It is thought that cancer vaccines can provide lasting anti-tumour immunity due to the body’s immunological memory.

In 2010, the FDA approved the first therapeutic cancer vaccine, sipuleucel-T (Provenge®), to treat metastatic prostate cancer. In the UK, therapeutic cancer vaccines are mostly available through participating in clinical trials. Current vaccines being investigated include antigen vaccines, whole cancer cell vaccines, dendritic cell vaccines, DNA vaccines, and anti-idiotype vaccines. Oncolytic virus vaccines and nanocarrier vaccines are also under investigation.

Although mABs and cytokine approaches have become standard in treating various cancers, other immunotherapies, such as vaccines, combined immunotherapies and cell-based approaches, remain in their infancy.

 

What is next for cancer research and cancer immunotherapy?

 

Of course, there are many other challenges to overcome in the immunotherapy fight against cancer.

 

We have yet to discover why some types of cancer respond better to immunotherapy, why clinical outcomes vary between patients with the same cancer type, and how tumours become resistant to immunotherapies.

 

Patient safety remains a concern, since an artificially modulated immune system has the potential to cause life-threatening adverse events. In addition, since only some of the side effects of these new treatments are known, other side effects may remain untreated.

However, with the recent developments in the field of immuno-oncology, immunotherapies now offer effective management of various cancer types, increasing the number of options available to the oncologist. Heightened interest in this field also means that novel immunotherapy techniques are continuously being investigated. This will, hopefully, produce treatments that could further revolutionise the way we treat cancer. Expect big breakthroughs from the leading pharmaceutical and biotechnology companies in this sector!

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